The aim of this research program is to investigate mechanisms of protective immunity and immunopathology in schistosomiasis with the ultimate goal of immunologic intervention. Progress was achieved in the following areas during the year. A) Prevention of egg granuloma formation with IL-12. The cytokine IL-12 was shown to block pulmonary egg pathology when given at the same time as granuloma formation and to prophylactically immunize against pathology when used in conjunction with egg immunization. B) Effects of upregulatory and downregulatory cytokines on vaccine- induced immunity. IL-12 when given at the time of vaccination with irradiated cercariae was shown to markedly enhance protective immunity. Conversely, the reduced immunity of vaccinated P-strain mice and C57BL/6 mice immunized with dead antigen via the intramuscular or intravenous as opposed to protective intradermal routes was shown to be associated with the production of the downregulatory cytokines IL-4 and IL-10 and TGF-beta, respectively. C) Mechanism of killing of schistosomula by cytokine-activated human macrophages and endothelial cells. Cytokine activated human macrophages were shown to kill schistosomula via a novel nitrogen oxide, respiratory burst independent mechanism.